Department of Spine Surgery, Orthopedics Hospital affiliated to the Second Bethune Hospital, Jilin University, Changchun 130041, ChinaDepartment of Pediatrics, University of Louisville School of Medicine, Louisville, KY 40202, USADepartment of Anatomical Sciences and Neurobiology, University of Louisville School of Medicine, Louisville, KY 40202, USA

Abstract

Abusive head trauma (AHT) is the leading cause of death from trauma in infants and young children. An AHT animal model was developed on 12-day-old mice subjected to 90° head extension-flexion sagittal shaking repeated 30, 60, 80, and 100 times. The mortality and time until return of consciousness were dependent on the number of repeats and severity of the injury. Under 60 times of repeated head shakings, the pups demonstrated apnea and/or bradycardia immediately after injury. Acute oxygen desaturation was observed by pulse oximetry during respiratory and cardiac suppression. The cerebral blood perfusion was assessed by laser speckle contrast analysis (LASCA) using the PeriCam PSI system. There was a severe reduction in cerebral blood perfusion immediately after the trauma that did not significantly improve within 24 hours. The injured mice began to experience reversible sensorimotor function at 9 days post-injury (dpi) which completely recovered at 28 dpi. However, cognitive deficits and anxiety-like behavior remained. Subdural/subarachnoid hemorrhage, damage to the brain-blood barrier, and parenchymal edema were found in all pups subjected to 60 insults. Pro-inflammatory response and reactive gliosis were up-regulated 3 dpi. Degenerated neurons were found in the cerebral cortex and olfactory tubercles at 30 dpi. This mouse model of repetitive brain injury by rotational head acceleration-deceleration partially mimics the major pathophysiological and behavioral events that occur in children with AHT. The resultant hypoxia/ischemia suggests a potential mechanism underlying the secondary rotational acceleration-deceleration induced brain injury in developing mice.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

Eloise Mikkonen from the University of Tampere, Finland, is part of a collaborative project investigating a connection between herpes simplex virus and Alzheimer’s disease. Thanks to a Travelling Fellowship from DMM, she visited her collaborators in Umeå University, Sweden, and the team have now published their work in DMM. Read more on her story here.

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